Does Increasing Oxygen Nurture Your Symptomatic Ischemic Ulcer Sufficiently?

Rationale: Diabetes is a major healthcare problem with a high incidence and morbidity. Diabetic foot ulcers (DFUs) are a major complication of diabetes, often associated with peripheral arterial occlusive disease. Currently available evidence shows HyperBaric Oxygen Therapy (HBOT) can reduce major amputation rate, but clinicians remain sceptical about the (cost-) effectiveness and feasibility of HBOT for ischaemic DFUs in clinical practice. Therefore, international vascular surgeons and HBOT-physicians feel a strong need for a sufficiently powered clinical trial to determine whether and how many HBOT-sessions may be a (cost-) effective adjunctive treatment to ischaemic DFUs.
Objective: The primary objective is to assess the (cost-) effectiveness of HBOT in addition to standard wound care and vascular surgical treatment for patients with a DFU and leg ischaemia.
Study design: An international, multi-arm multi-stage (MAMS) design is chosen to conduct an efficient randomised clinical trial. At a planned interim analysis the best performing study arm(s) will be chosen to continue.
Study population: We need up to 544 patients with a Meggitt-Wagner stage 3 or 4 DFU and proven peripheral ischaemia.
Intervention: Patients will be randomised to receive standard care (wound treatment and surgical interventions following international guidelines) with either 0, 20, 30 or at least 40 sessions of HBOT. These sessions will compromise 90-120 minutes of HBOT at a pressure of 2.2-2.5 ATA according to international standards.
Main study parameters/endpoints: The primary endpoint is major amputation rate after 12 months. Secondary objectives are amputation-free survival, wound healing, health-related quality of life and cost-effectiveness of the interventions.

HBOT will prevent amputations in patients with ischaemic DFUs

Patients from each (remaining) study arm will be monitored up to 36 months after randomisation. At the start of the trial, patients’ baseline characteristics will be obtained. Pain scores will be collected through first phase of the trial. Questionnaires will be completed at baseline and will be sent to the patients’ home after 3 months and 1 year. Amputation rate, ulcer recurrence, additional interventions, mortality, adverse events and costs will be monitored after 1 year and 3 years.

Patients allocated to the intervention group will receive 20, 30 or a minimum of 40 sessions of HBOT adjunctive to standard care, as determined by the randomisation. In the group with at least 40 treatments, the patients will receive 40 treatments. After these 40 treatments, the hyperbaric physician may decide on clinical grounds whether it seems wise to continue the HBOT treatment up to a maximum of 60 sessions. A HBOT session will take 90 to 120 minutes at 2.2-2.5 ATA. Besides the 90-120 minutes of treatment, approximately 20 minutes are required for compression and decompression. During the treatment session, the patients will breathe 100% FiO2 except for 3 blocks of 5 minutes during which atmospheric air will be administered to prevent oxygen intoxication.